749 research outputs found
Hot Yoga Establishments in Local Communities Serving Pregnant Women: A Pilot Study on the Health Implications of its Practice and Environmental Conditions
Hot yoga establishments have been increasing in popularity in local communities. Studios may support participation among pregnant women though no clinical studies currently exist that examine prenatal hot yoga effects. The pilot study described in this article aimed to assess the spread of prenatal hot yoga and to provide information on the environmental conditions and practices of those who engage in hot yoga within a local community. A thermal environment meter was used to measure ambient air conditions during three 90-minute hot yoga classes. Mothers who practiced prenatal hot yoga were more likely than non-hot yoga practitioners to have someone aside from an obstetrician/gynecologist discuss prenatal exercise safety with them. Prenatal public health education campaigns need to he refined. Public health officials and obstetricians/gynecologists need to he aware that those who engage in a hot yoga practice are more likely to trust someone other than their health care provider or public health professional regarding safety of this practice
Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies
PURPOSE: The prognostic and predictive value of intrinsic subtypes in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with endocrine therapy and ribociclib (RIB) is currently unknown. We evaluated the association of intrinsic subtypes with progression-free survival (PFS) in the MONALEESA trials. METHODS: A retrospective and exploratory PAM50-based analysis of tumor samples from the phase III MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials was undertaken. The prognostic relationship of PAM50-based subtypes with PFS and risk of disease progression by subtype and treatment were evaluated using a multivariable Cox proportional hazards model, adjusting for age, prior chemotherapy, performance status, visceral disease, bone-only metastases, histological grade, number of metastatic sites, prior endocrine therapy, and de novo metastatic disease. RESULTS: Overall, 1,160 tumors from the RIB (n = 672) and placebo (n = 488) cohorts were robustly profiled. Subtype distribution was luminal A (LumA), 46.7%; luminal B (LumB), 24.0%; normal-like, 14.0%; HER2-enriched (HER2E), 12.7%; and basal-like, 2.6% and was generally consistent across treatment arms and trials. The associations between subtypes and PFS were statistically significant in both arms (P < .001). The risks of disease progression for LumB, HER2E, and basal-like subtypes were 1.44, 2.31, and 3.96 times higher compared with those for LumA, respectively. All subtypes except basal-like demonstrated significant PFS benefit with RIB. HER2E (hazard ratio [HR], 0.39; P < .0001), LumB (HR, 0.52; P < .0001), LumA (HR, 0.63; P = .0007), and normal-like (HR, 0.47; P = .0005) subtypes derived benefit from RIB. Patients with basal-like subtype (n = 30) did not derive benefit from RIB (HR, 1.15; P = .77). CONCLUSION: In this retrospective exploratory analysis of hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer, each intrinsic subtype exhibited a consistent PFS benefit with RIB, except for basal-like
A Mixed-Method Study to Determine the Benefits of Periconceptional Folic Acid Supplementation and Effects of Folic Acid Deficiency in Mothers on Birth Outcomes.
BACKGROUND: Evidence from high income countries shows mothers who are supplemented with folic acid in their periconceptional period and early pregnancy have significantly reduced adverse outcomes like birth defects. However, in India there is a paucity of data on association of birth defects and folic acid supplementation. We identified a few important questions to be answered using separate scientific methods and then planned to triangulate the information. OBJECTIVE: In this paper, we describe the protocol of our study that aims to determine the association of folic acid and pregnancy outcomes like neural tube defects (NTDs) and orofacial clefts (OFCs). We decided to fill the gaps in knowledge from India to determine public health consequences of folic acid deficiency and factors influencing dietary and periconceptional consumption of folic acid. METHODS: The proposed study will be carried out in five stages and will examine the questions related to folic acid deficiency across selected locations in South and North India. The study will be carried out over a period of 4 years through the hierarchical evidence-based approach. At first a systematic review was conducted to pool the current birth prevalence of NTDs and orofacial clefts OFCs in India. To investigate the population prevalence, we plan to use the key informant method to determine prevalence of NTDs and OFCs. To determine the normal serum estimates of folic acid, iron, and vitamin B12 among Indian women (15-35 years), we will conduct a population-based, cross-sectional study. We will further strengthen the evidence of association between OFCs and folic acid by conducting a hospital-based, case-control study across three locations of India. Lastly, using qualitative methods we will understand community and health workers perspective on factors that decide the intake of folic acid supplements. RESULTS: This study will provide evidence on the community prevalence of birth defects and prevalence folic acid and vitamin B12 deficiency in the community. The case-control study will help understand the association of folic acid deficiency with OFCs. CONCLUSIONS: The results from this study are intended to strengthen the evidence base in childhood disability for planning and policy initiatives
Climate Change and Heat Stress Tolerance in Chickpea
Chickpea (Cicer arietinum L.) is a cool-season food legume and suffers heavy yield losses when exposed to heat stress at the reproductive (flowering and podding) stage. Heat stress is increasingly becoming a severe constraint to chickpea production due to the changing scenario of chickpea cultivation and expected overall increase in global temperatures due to climate change. A temperature of 35 °C was found to be critical in differentiating heat-tolerant and heat-sensitive genotypes in chickpea under field conditions. Large genetic variations exist in chickpea for reproductive-stage heat tolerance. Many heat-tolerant genotypes have been identified through screening of germplasm/breeding lines under heat stress conditions in the field. A heat-tolerant breeding line ICCV 92944 has been released in two countries (as Yezin 6 in Myanmar and JG 14 in India) and is performing well under late-sown conditions. Heat stress during the reproductive phase adversely affects pollen viability, fertilization, pod set, and seed development, leading to abscission of flowers and pods, and substantial losses in grain yield. Studies on physiological mechanisms and genetics of heat tolerance, and identification of molecular markers and candidate genes for heat tolerance, are in progress. The information generated from these studies will help in developing effective and efficient breeding strategies for heat tolerance. The precision and efficiency of breeding programs for improving heat tolerance can be enhanced by integrating novel approaches, such as marker-assisted selection, rapid generation turnover, and gametophytic selection. Chickpea cultivars with enhanced heat tolerance will minimize yield losses in cropping systems/growing conditions where the crop is exposed to heat stress at the reproductive stage
Peroxisome proliferator-activated receptor gamma and spermidine/spermine N(1)-acetyltransferase gene expressions are significantly correlated in human colorectal cancer
BACKGROUND: The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that regulates adipogenic differentiation and glucose homeostasis. Spermidine/spermine N(1)-acetyltransferase (SSAT) and ornithine decarboxylase (ODC) are key enzymes involved in the metabolism of polyamines, compounds that play an important role in cell proliferation. While the PPARγ role in tumour growth has not been clearly defined, the involvement of the altered polyamine metabolism in colorectal carcinogenesis has been established. In this direction, we have evaluated the PPARγ expression and its relationship with polyamine metabolism in tissue samples from 40 patients operated because of colorectal carcinoma. Since it is known that the functional role of K-ras mutation in colorectal tumorigenesis is associated with cell growth and differentiation, polyamine metabolism and the PPARγ expression were also investigated in terms of K-ras mutation. METHODS: PPARγ, ODC and SSAT mRNA levels were evaluated by reverse transcriptase and real-time PCR. Polyamines were quantified by high performance liquid chromatography (HPLC). ODC and SSAT activity were measured by a radiometric technique. RESULTS: PPARγ expression, as well as SSAT and ODC mRNA levels were significantly higher in cancer as compared to normal mucosa. Tumour samples also showed significantly higher polyamine levels and ODC and SSAT activities in comparison to normal samples. A significant and positive correlation between PPARγ and the SSAT gene expression was observed in both normal and neoplastic tissue (r = 0.73, p < 0.0001; r = 0.65, p < 0.0001, respectively). Moreover, gene expression, polyamine levels and enzymatic activities were increased in colorectal carcinoma samples expressing K-ras mutation as compared to non mutated K-ras samples. CONCLUSION: In conclusion, our data demonstrated a close relationship between PPARγ and SSAT in human colorectal cancer and this could represent an attempt to decrease polyamine levels and to reduce cell growth and tumour development. Therefore, pharmacological activation of PPARγ and/or induction of SSAT may represent a therapeutic or preventive strategy for treating colorectal cancer
Environmental and Economic Impacts of Growing Certified Organic Coffee in Colombia
According to advocates, eco-certification can improve developing country farmers' environmental and economic performance. However, these notional benefits can be undercut by self-selection: the tendency of relatively wealthy farmers already meeting eco-certification standards to disproportionately participate. Empirical evidence on this matter is scarce. Using original farm-level survey data along with matching and difference-in-differences matching models, we analyze the producer-level effects of organic coffee certification in southeast Colombia. We find that certification improves coffee growers' environmental performance. It significantly reduces sewage disposal in the fields and increases the adoption of organic fertilizer. However, we are not able to discern economic benefits
Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm
Background: Polyamine metabolism has a critical role in cell death and proliferation representing a potential
target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and
its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in
anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO
enzyme.
Methods: BC tissue samples were analyzed for SMO transcript level and SMO activity. Student’s t test was applied
to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling
analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed
by in vitro experiments, were examined.
Results: Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples
compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their
inhibition properties showed that both were good inhibitors.
Conclusions: This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a
remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition
properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials
Reactive Oxygen Species Hydrogen Peroxide Mediates Kaposi's Sarcoma-Associated Herpesvirus Reactivation from Latency
Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent
infection in the host following an acute infection. Reactivation from latency
contributes to the development of KSHV-induced malignancies, which include
Kaposi's sarcoma (KS), the most common cancer in untreated AIDS patients,
primary effusion lymphoma and multicentric Castleman's disease. However,
the physiological cues that trigger KSHV reactivation remain unclear. Here, we
show that the reactive oxygen species (ROS) hydrogen peroxide
(H2O2) induces KSHV reactivation from latency through
both autocrine and paracrine signaling. Furthermore, KSHV spontaneous lytic
replication, and KSHV reactivation from latency induced by oxidative stress,
hypoxia, and proinflammatory and proangiogenic cytokines are mediated by
H2O2. Mechanistically, H2O2
induction of KSHV reactivation depends on the activation of mitogen-activated
protein kinase ERK1/2, JNK, and p38 pathways. Significantly,
H2O2 scavengers N-acetyl-L-cysteine (NAC), catalase
and glutathione inhibit KSHV lytic replication in culture. In a mouse model of
KSHV-induced lymphoma, NAC effectively inhibits KSHV lytic replication and
significantly prolongs the lifespan of the mice. These results directly relate
KSHV reactivation to oxidative stress and inflammation, which are physiological
hallmarks of KS patients. The discovery of this novel mechanism of KSHV
reactivation indicates that antioxidants and anti-inflammation drugs could be
promising preventive and therapeutic agents for effectively targeting KSHV
replication and KSHV-related malignancies
A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective chemopreventive agents for colorectal neoplasia. Polymorphisms in NSAID targets or metabolizing enzymes may affect NSAID efficacy or toxicity. We conducted a literature review to summarize current evidence of gene-drug interactions between NSAID use and polymorphisms in COX1, COX2, ODC, UGT1A6 and CYP2C9 on risk of colorectal neoplasia by searching OVID and PubMed. Of 134 relevant search results, thirteen investigated an interaction. One study reported a significant interaction between NSAID use and the COX1 Pro17Leu polymorphism (P=0.03) whereby the risk reduction associated with NSAID use among homozygous wild-type genotypes was not observed among NSAID users with variant alleles. Recent pharmacodynamic data support the potential for gene-drug interactions for COX1 Pro17Leu. Statistically significant interactions have also been reported for ODC (315G>A), UGT1A6 (Thr181Ala+Arg184Ser or Arg184Ser alone), and CYP2C9 (*2/*3). No statistically significant interactions have been reported for polymorphisms in COX2; however, an interaction with COX2 -765G>C approached significance (P=0.07) in one study. Among seven remaining studies, reported interactions were not statistically significant for COX1, COX2 and ODC gene polymorphisms. Most studies were of limited sample size. Definitions of NSAID use differed substantially between studies. The literature on NSAID-gene interactions to date is limited. Reliable detection of gene-NSAID interactions will require greater sample sizes, consistent definitions of NSAID use and evaluation of clinical trial subjects of chemoprevention studies
Triple-GEM discharge probability studies at CHARM: Simulations and experimental results
The CMS muon system in the region with 2.03<|η|<2.82 is characterized by a very harsh radiation environment which can generate hit rates up to 144 kHz/cm and an integrated charge of 8 C/cm over ten years of operation. In order to increase the detector performance and acceptance for physics events including muons, a new muon station (ME0) has been proposed for installation in that region. The technology proposed is Triple—Gas Electron Multiplier (Triple-GEM), which has already been qualified for the operation in the CMS muon system. However, an additional set of studies focused on the discharge probability is necessary for the ME0 station, because of the large radiation environment mentioned above. A test was carried out in 2017 at the Cern High energy AcceleRator Mixed (CHARM) facility, with the aim of giving an estimation of the discharge probability of Triple-GEM detectors in a very intense radiation field environment, similar to the one of the CMS muon system. A dedicated standalone Geant4 simulation was performed simultaneously, to evaluate the behavior expected in the detector exposed to the CHARM field. The geometry of the detector has been carefully reproduced, as well as the background field present in the facility. This paper presents the results obtained from the Geant4 simulation, in terms of sensitivity of the detector to the CHARM environment, together with the analysis of the energy deposited in the gaps and of the processes developed inside the detector. The discharge probability test performed at CHARM will be presented, with a complete discussion of the results obtained, which turn out to be consistent with measurements performed by other groups
- …